tbuckley/cabot-search huggingface dataset:
Public Health Response to Clusters of Rapid HIV Transmission Among Hispanic or Latino Gay, Bisexual, and Other Men Who Have Sex with Men — Metropolitan Atlanta, Georgia, 2021–2022
Authors: Carlos Saldana, David C. Philpott, Daniel E. Mauck, Rebecca B. Hershow, Eleanor Garlow, Jenna Gettings, Dorian Freeman, Anne Marie France, Erica N. Johnson, Agha Ajmal, Dena Elimam, Karrie Reed, Alana Sulka, Jose F. Adame, Jonny F. Andía, Mariana Gutierrez, Mabel Padilla, Nathalie Gonzalez Jimenez, Craig Hayes, Robert P. McClung, Valeria D. Cantos, David P. Holland, Jane Yoon Scott, Alexandra M. Oster, Kathryn G. Curran, Rashida Hassan, Pascale Wortley
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

These authors contributed equally to this report.† Partner services interviews are completed by health departments for eligible persons with a newly diagnosed HIV infection and, potentially, after a person with known HIV infection is identified as part of a cluster.Interviews are completed to ensure that persons with HIV infection are linked to care and to obtain information about
Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax
Authors: Alexander Waclawiczek, Aino-Maija Leppä, Simon Renders, Karolin Stumpf, Cecilia Reyneri, Barbara Betz, Maike Janssen, Rabia Shahswar, Elisa Donato, Darja Karpova, Vera Thiel, Julia M. Unglaub, Susanna Grabowski, Stefanie Gryzik, Lisa Vierbaum, Richard F. Schlenk, Christoph Röllig, Michael Hundemer, Caroline Pabst, Michael Heuser, Simon Raffel, Carsten Müller-Tidow, Tim Sauer, Andreas Trumpp
Journal: Cancer Discovery (2023)

The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based "Mediators of apoptosis combinatorial score" (MAC-Score) linking the ratio of protein expression of BCL2, BCL-xL, and MCL1 in LSCs. MAC scoring predicts initial response with a positive predictive value of more than 97% associated with increased event-free survival. In summary, combinatorial levels of BCL2 family members in AML-LSCs are a key denominator of response, and MAC scoring reliably predicts patient response to 5-AZA/VEN. Venetoclax/azacitidine treatment has become an alternative to standard chemotherapy for patients with AML. However, prediction of response to treatment is hampered by the lack of clinically useful biomarkers. Here, we present easy-to-implement MAC scoring in LSCs as a novel strategy to predict treatment response and facilitate clinical decision-making. This article is highlighted in the In This Issue feature, p. 1275.
Safety and performance of a novel implantable sensor in the inferior vena cava under acute and chronic intravascular volume modulation
Authors: William Stephen Sheridan, Friedrich Wetterling, Jeffrey Moore Testani, Barry A. Borlaug, Marat Fudim, Kevin Damman, Alastair Gray, Peter Gaines, Martin Poloczek, Stephen Madden, James Tucker, Teresa Buxo, Robert Gaul, Louise Corcoran, Fiachra Sweeney, Daniel Burkhoff
Journal: European Journal of Heart Failure (2023)

ABSTRACT Aims The management of congestion is one of the key treatment targets in heart failure. Assessing congestion is, however, difficult. The purpose of this study was to investigate the safety and dynamic response of a novel, passive, inferior vena cava (IVC) sensor in a chronic ovine model. Methods and results A total of 20 sheep divided into three groups were studied in acute and chronic in vivo settings. Group I and Group II included 14 sheep in total with 12 sheep receiving the sensor and two sheep receiving a control device (IVC filter). Group III included an additional six animals for studying responses to volume challenges via infusion of blood and saline solutions. Deployment was 100% successful with all devices implanted; performing as expected with no device‐related complications and signals were received at all observations. At similar volume states no significant differences in IVC area normalized to absolute area range were measured (55 ± 17% on day 0 and 62 ± 12% on day 120, p = 0.51). Chronically, the sensors were completely integrated with a thin, reendothelialized neointima with no loss of sensitivity to infused volume. Normalized IVC area changed significantly from 25 ± 17% to 43 ± 11% ( p = 0.007) with 300 ml infused. In contrast, right atrial pressure required 1200 ml of infused volume prior to a statistically significant change from 3.1 ± 2.6 mmHg to 7.5 ± 2.0 mmHg ( p = 0.02). Conclusion In conclusion, IVC area can be measured remotely in real‐time using a safe, accurate, wireless, and chronic implantable sensor promising to detect congestion with higher sensitivity than filling pressures.
Regorafenib, Ipilimumab, and Nivolumab for Patients With Microsatellite Stable Colorectal Cancer and Disease Progression With Prior Chemotherapy
Authors: Marwan Fakih, Jaideep Sandhu, Dean Lim, Xiaochen Li, Sierra Li, Chongkai Wang
Journal: JAMA Oncology (2023)

Immunotherapy combinations with activity in patients with microsatellite stable (MSS) metastatic colorectal cancer need to be identified.
Intercellular hif1α reprograms mammary progenitors and myeloid immune evasion to drive high-risk breast lesions
Authors: Irene Bertolini, Michela Perego, Yulia Nefedova, Cindy Lin, Andrew Milcarek, Peter Vogel, Jagadish C. Ghosh, Andrew V. Kossenkov, Dario C. Altieri
Journal: Journal of Clinical Investigation (2023)

The origin of breast cancer, whether primary or recurrent, is unknown. Here, we show that invasive breast cancer cells exposed to hypoxia release small extracellular vesicles (sEVs) that disrupt the differentiation of normal mammary epithelia, expand stem and luminal progenitor cells, and induce atypical ductal hyperplasia and intraepithelial neoplasia. This was accompanied by systemic immunosuppression with increased myeloid cell release of the alarmin S100A9 and oncogenic traits of epithelial-mesenchymal transition, angiogenesis, and local and disseminated luminal cell invasion in vivo. In the presence of a mammary gland driver oncogene (MMTV-PyMT), hypoxic sEVs accelerated bilateral breast cancer onset and progression. Mechanistically, genetic or pharmacologic targeting of hypoxia-inducible factor-1α (HIF1α) packaged in hypoxic sEVs or homozygous deletion of S100A9 normalized mammary gland differentiation, restored T cell function, and prevented atypical hyperplasia. The transcriptome of sEV-induced mammary gland lesions resembled luminal breast cancer, and detection of HIF1α in plasma circulating sEVs from luminal breast cancer patients correlated with disease recurrence. Therefore, sEV-HIF1α signaling drives both local and systemic mechanisms of mammary gland transformation at high risk for evolution to multifocal breast cancer. This pathway may provide a readily accessible biomarker of luminal breast cancer progression.
Comparison of Health Care Worker Satisfaction Before vs After Implementation of a Communication and Optimal Resolution Program in Acute Care Hospitals
Authors: Andrew I. Friedson, Abigail Humphreys, Florence LeCraw, Barbara Pelletreau, Priscilla Vierra, Thomas A. Mroz
Journal: JAMA Network Open (2023)

This case-control study investigates the association between a communication and optimal resolution program to address unexpected adverse patient outcomes and measures of health care worker satisfaction.
ASS1-Mediated Reductive Carboxylation of Cytosolic Glutamine Confers Ferroptosis Resistance in Cancer Cells
Authors: Qiangsheng Hu, Jie Dai, Zheng Zhang, Huansha Yu, Jing Zhang, Xinsheng Zhu, Yi Qin, Lele Zhang, Peng Zhang
Journal: Cancer Research (2023)

Induction of ferroptosis, a recently defined form of nonapoptotic cell death caused by iron-dependent lipid peroxidation, has emerged as an anticancer strategy. Erastin is a ferroptosis activator that promotes cell death that not only depends on the depletion of cellular cysteine but also relies on mitochondrial oxidative metabolism of glutamine. Here, we demonstrate that ASS1, a key enzyme involved in the urea cycle, plays a crucial role in ferroptosis resistance. Loss of ASS1 increased the sensitivity of non-small cell lung cancer (NSCLC) cells to erastin in vitro and decreased tumor growth in vivo. Metabolomics analysis with stable isotope-labeled glutamine showed that ASS1 promotes reductive carboxylation of cytosolic glutamine and compromises the oxidative tricarboxylic acid cycle from glutamine anaplerosis, reducing mitochondrial-derived lipid reactive oxygen species. Moreover, transcriptome sequencing showed that ASS1 activates the mTORC1-SREBP1-SCD5 axis to promote de novo monounsaturated fatty acid synthesis by using acetyl-CoA derived from the glutamine reductive pathway. Treating ASS1-deficient NSCLC cells with erastin combined with arginine deprivation significantly enhanced cell death compared with either treatment alone. Collectively, these results reveal a previously unknown regulatory role of ASS1 in ferroptosis resistance and provide a potential therapeutic target for ASS1-deficient NSCLC.ASS1 promotes reductive carboxylation of glutamine and confers ferroptosis resistance, providing multiple treatment options for ASS1-deficient non-small cell lung cancer.
Platelet-Derived MicroRNAs Regulate Cardiac Remodeling After Myocardial Ischemia
Authors: Jan Philipp Schütte, Mailin-Christin Manke, Katherina Hemmen, Patrick Münzer, Barbara F. Schörg, Gustavo Campos Ramos, Michaela Pogoda, Valerie Dicenta, Sabrina H.L. Hoffmann, Jürgen Pinnecker, Ferdinand Kollotzek, Monika Zdanyte, Karin A.L. Mueller, Yogesh Singh, Andreas F. Mack, Bernd Pichler, Florian Lang, Bernhard Nieswandt, Meinrad Gawaz, Katrin G. Heinze, Nicolas Casadei, Oliver Borst
Journal: Circulation Research (2023)

Background: Platelets can infiltrate ischemic myocardium and are increasingly recognized as critical regulators of inflammatory processes during myocardial ischemia and reperfusion (I/R). Platelets contain a broad repertoire of microRNAs (miRNAs), which, under certain conditions such as myocardial ischemia, may be transferred to surrounding cells or released into the microenvironment. Recent studies could demonstrate that platelets contribute substantially to the circulating miRNA pool holding the potential for so far undiscovered regulatory functions. The present study aimed to determine the role of platelet-derived miRNAs in myocardial injury and repair following myocardial I/R. Methods: In vivo model of myocardial I/R, multimodal in vivo and ex vivo imaging approaches (light-sheet fluorescence microscopy, positron emission tomography and magnetic resonance imaging, speckle-tracking echocardiography) of myocardial inflammation and remodeling, and next-generation deep sequencing analysis of platelet miRNA expression. Results: In mice with a megakaryocyte/platelet-specific knockout of pre-miRNA processing ribonuclease Dicer , the present study discloses a key role of platelet-derived miRNAs in the tightly regulated cellular processes orchestrating left ventricular remodeling after myocardial I/R following transient left coronary artery ligation. Disruption of the miRNA processing machinery in platelets by deletion of Dicer resulted in increased myocardial inflammation, impaired angiogenesis, and accelerated development of cardiac fibrosis, culminating in an increased infarct size by d7 that persisted through d28 of myocardial I/R. Worsened cardiac remodeling after myocardial infarction in mice with a platelet-specific Dicer deletion resulted in an increased fibrotic scar formation and distinguishably increased perfusion defect of the apical and anterolateral wall at day 28 post-myocardial infarction. Altogether, these observations culminated in an impaired left ventricular function and hampered long-term cardiac recovery after experimental myocardial infarction and reperfusion therapy. Treatment with the P2Y 12 (P2Y purinoceptor 12) antagonist ticagrelor completely reversed increased myocardial damage and adverse cardiac remodeling observed in Dicer Pf4∆/Pf4∆ mice. Conclusions: The present study discloses a critical role of platelet-derived miRNA in myocardial inflammation and structural remodeling processes following myocardial I/R.
Evaluation of Alisertib Alone or Combined With Fulvestrant in Patients With Endocrine-Resistant Advanced Breast Cancer
Authors: Tufia C. Haddad, Vera J. Suman, Antonino B. D’Assoro, Jodi M. Carter, Karthik V. Giridhar, Brendan P. McMenomy, Katelyn Santo, Erica L. Mayer, Meghan S. Karuturi, Aki Morikawa, P. Kelly Marcom, Claudine J. Isaacs, Sun Young Oh, Amy S. Clark, Ingrid A. Mayer, Khandan Keyomarsi, Timothy J. Hobday, Prema P. Peethambaram, Ciara C. O’Sullivan, Roberto A. Leon-Ferre, Minetta C. Liu, James N. Ingle, Matthew P. Goetz
Journal: JAMA Oncology (2023)

Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. The safety and preliminary efficacy of alisertib was demonstrated in early-phase trials; however, its activity in CDK 4/6i-resistant MBC is unknown.
Efficacy and safety of roflumilast cream for chronic plaque psoriasis with facial/neck and intertriginous area involvement: a post hoc analysis from a randomized controlled trial
Authors: Zoe D Draelos, David N Adam, H Chih-ho Hong, Mark G Lebwohl, Charles W Lynde, Walter K Nahm, Kim A Papp, David M Pariser, Linda Stein Gold, Daniel Stewart, Robert C Higham, David R Berk, David Krupa, Patrick Burnett
Journal: British Journal of Dermatology (2023)

This post hoc analysis evaluated efficacy and safety of roflumilast cream in patients with psoriasis involving the face/neck or intertriginous areas from a phase IIb trial. Of 331 patients enrolled in the phase IIb trial, 160 had psoriasis involving the face/neck and/or intertriginous areas. Once-daily roflumilast cream was well tolerated with efficacy across multiple endpoints in these patients.
Longitudinal effect of disease‐modifying therapy on left ventricular diastolic function in children with sickle cell anemia
Authors: Parul Rai, Victoria I. Okhomina, Guolian Kang, Hugo R. Martinez, Jane S. Hankins, Vijaya Joshi
Journal: American Journal of Hematology (2023)

Cardiac abnormalities seen in sickle cell anemia (SCA) include diastolic dysfunction, which has been shown to be associated with high morbidity and early mortality. The effect of disease-modifying therapies (DMT) on diastolic dysfunction is poorly understood. We prospectively evaluated the effects of hydroxyurea and monthly erythrocyte transfusions on diastolic function parameters over 2 years. A total of 204 subjects with HbSS or HbSβ0-thalassemia (mean age 11 ± 3.7 years), unselected for disease severity, had diastolic function assessed with surveillance echocardiograms twice, 2 years apart. During this 2-year observation period, 112 participants received DMTs (hydroxyurea, n = 72, monthly erythrocyte transfusions, n = 40), 34 initiated hydroxyurea, and 58 did not receive any DMT. The entire cohort showed an increase in left atrial volume index (LAVi) of 3.40 ± 10.86 mL/m2, p = .001 over 2 years. This increase in LAVi was independently associated with anemia, high baseline E/e' or LV dilation. Individuals not exposed to DMT were younger (mean age 8.8 ± 2.9 years), but at baseline their prevalence of abnormal diastolic parameters was similar to that of the DMT-exposed participants who were older (mean age 12 ± 3.8 years). Participants on DMTs saw no improvement in diastolic function over the study period. In fact, participants on hydroxyurea saw a possible worsening in diastolic parameters (14% increase in LAVi and ~5% decrease in septal e') but also a ~9% decrease in fetal hemoglobin (HbF) levels. Further studies are needed to evaluate if exposure to DMT for a longer duration or achieving higher HbF might be beneficial in alleviating diastolic dysfunction.
Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma
Authors: Robert E. Schoen, Lisa A. Boardman, Marcia Cruz-Correa, Ajay Bansal, David Kastenberg, Chin Hur, Lynda Dzubinski, Sharon F. Kaufman, Luz M. Rodriguez, Ellen Richmond, Asad Umar, Eva Szabo, Andres Salazar, John McKolanis, Pamela Beatty, Reetesh K. Pai, Aatur D. Singhi, Camille M. Jacqueline, Riyue Bao, Brenda Diergaarde, Ryan P. McMurray, Carrie Strand, Nathan R. Foster, David M. Zahrieh, Paul J. Limburg, Olivera J. Finn
Journal: Clinical Cancer Research (2023)

To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation.
Minimal Residual Disease Data in Hematologic Malignancy Drug Applications and Labeling: An FDA Perspective
Authors: Andrea C. Baines, Maryam Sarraf Yazdy, Yvette L. Kasamon, Rachel Ershler, Emily Y. Jen, Bindu Kanapuru, Nicholas C. Richardson, Ashley Lane, Theresa Carioti, Marc R. Theoret, Richard Pazdur, Nicole J. Gormley
Journal: Clinical Cancer Research (2023)

Abstract Minimal residual disease (MRD) is increasingly used as a prognostic biomarker, a measure of clinical efficacy, and a guide for treatment decisions in various hematologic malignancies. We sought to characterize MRD data in registrational trials in hematologic malignancies submitted to the U.S. Food and Drug Administration (FDA) with the ultimate goal of expanding the utility of MRD data in future drug applications. We descriptively analyzed MRD data collected in registrational trials, including the type of MRD endpoint, assay, disease compartment(s) assessed, and the acceptance of MRD data in the U.S. prescribing information (USPI). Of 196 drug applications submitted between January 2014 and February 2021, 55 (28%) included MRD data. Of the 55 applications, MRD data was proposed by the Applicant for inclusion in the USPI in 41 (75%) applications but was included in only 24 (59%). Despite an increasing number of applications that proposed to include MRD data in the USPI, the acceptance rate decreased over time. Although MRD data have the potential to expedite drug development, our analysis identified challenges and specific areas for improvement, including assay validation, standardization of collection methods to optimize performance, and considerations in trial design and statistical methodology.
Steroid Dose and Duration, Immortal Time Bias, and Survival After High-grade Immune-Related Adverse Events—Reply
Authors: Olivier J. van Not, Rik J. Verheijden, Karijn P. M. Suijkerbuijk
Journal: JAMA Oncology (2023)

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<i>Notes from the Field:</i> Increase in Pediatric Invasive Group A <i>Streptococcus</i> Infections — Colorado and Minnesota, October–December 2022
Authors: Meghan Barnes, Erin Youngkin, Jennifer Zipprich, Kayla Bilski, Christopher J. Gregory, Samuel R. Dominguez, Erica Mumm, Melissa McMahon, Kathryn Como-Sabetti, Ruth Lynfield, Sopio Chochua, Jennifer Onukwube, Melissa Arvay, Rachel Herlihy
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

During fall 2022, a resurgence of invasive group A Streptococcus (iGAS) infection in children and adolescents was observed in two of CDC's Emerging Infections Program (EIP)* surveillance sites: Colorado (Denver metropolitan area) and Minnesota (entire state).This increase followed historic declines in invasive bacterial diseases during 2020, concurrent with mitigation strategies implemented during the COVID-19 pandemic † (1).Whereas reports of iGAS increased among all age groups, including adults, the increase among children and adolescents was notable, occurred earlier than seasonal increases during previous years, and accompanied a resurgence in hospitalizations for respiratory viral illnesses such as respiratory syncytial virus (RSV) and influenza.Viral infections, such as influenza and varicella, have been identified as risk factors for iGAS infection in children, adolescents, and adults (2) and can be reduced by vaccination.Surveillance for iGAS is conducted by 10 U.S. sites as part of EIP's Active Bacterial Core surveillance (ABCs).§ An analysis of cases among Colorado and Minnesota EIP site residents aged <18 years who met criteria for iGAS ¶ was conducted using ABCs data from the Colorado and Minnesota surveillance sites.Case counts, age distribution, and clinical characteristics of patients with iGAS infection were compared over three periods: baseline (January 1, 2016-December 31